DESCRIPTION: Previous work on this project has demonstrated that the vasospastic attacks of primary Raynaud's disease are triggered by cold hypersensitivity of peripheral vascular alpha(2)-adrenergic receptors. The investigators have also demonstrated familial aggregation of this disorder and found a genetic polymorphism in an alpha(2)-adrenoceptor gene that is twice as common in Raynaud's disease patients than in controls. The investigators therefore propose to verify this finding in a larger sample of patients with rigorous control groups and to determine if Raynaud's disease is actually inherited along with this genetic marker. Considerably less is known about the pathophysiology of Raynaud's phenomenon in scleroderma. Intimal proliferation, adventitial fibrosis, and endothelial injury have been demonstrated in digital blood vessels of scleroderma patients. However, luminal narrowing is not sufficient, by itself, to explain Raynaud's phenomenon because some asymptomatic individuals show equal degrees of luminal encroachment. The investigators propose to determine if alpha(2)-adrenergic and/or endothelial function is altered in patients with Raynaud's phenomenon and scleroderma. Patients will be screened with a heating and reactive hyperemia test to detect structural vascular changes in the fingers. Then, the finger blood flow responses to intra-arterial alpha(1) and alpha(2)-adrenergic agonists will be determined in scleroderma patients and normal volunteers. The effects of local cooling on adrenergic responsiveness will then be studied using similar methods. They will then study the role of endothelial function in scleroderma using drugs that act on specific segments of the vascular endothelial pathway and drugs that act through nonendothelial mechanisms. Finally, this research will determine if adrenergic antagonists or a compound that releases nitric oxide from vascular endothelium can actually block Raynaud's attacks induced in the laboratory in scleroderma patients.